A Trial Investigating the Efficacy and Safety of Insulin Degludec/Insulin Aspart Once Daily Plus Insulin Aspart for the Remaining Meals Versus Insulin Detemir Once or Twice Daily Plus Meal Time Insulin Aspart in Children and Adolescents With Type 1 Diabetes Mellitus

This trial is conducted in Asia, Europe and North and South America. The aim of the trial is to investigate the efficacy and safety of insulin degludec/insulin aspart once daily plus insulin aspart for the remaining meals in children and adolescents with type 1 diabetes mellitus.

Study Overview

• Status: Completed
• Conditions: Diabetes; Diabetes Mellitus, Type 1
• Intervention / Treatment: Drug: insulin degludec/insulin aspart; Drug: insulin aspart; Drug: insulin aspart; Drug: insulin detemir

• Study Type: Interventional
• Enrollment (Actual): 362
• Phase: Phase 3

Contacts and Locations

Study Locations

• Belgium
  • Brussels, Belgium, 1090
    • Novo Nordisk Investigational Site
  • Brussels, Belgium, 1200
    • Novo Nordisk Investigational Site
  • Leuven, Belgium, 3000
    • Novo Nordisk Investigational Site
• Brazil
  • Parana
    • Curitiba, Parana, Brazil, 80810-040
      • Novo Nordisk Investigational Site
  • Rio Grande Do Sul
    • Porto Alegre, Rio Grande Do Sul, Brazil, 91350-250
      • Novo Nordisk Investigational Site
  • Sao Paulo
    • São Paulo, Sao Paulo, Brazil, 01228-200
      • Novo Nordisk Investigational Site
• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V6H 3V4
      • Novo Nordisk Investigational Site
  • Ontario
    • London, Ontario, Canada, N6A 5W9
      • Novo Nordisk Investigational Site
    • Mississauga, Ontario, Canada, L5B 1B8
      • Novo Nordisk Investigational Site
  • Quebec
    • Montreal, Quebec, Canada, HIT 2M4
      • Novo Nordisk Investigational Site
    • Montreal, Quebec, Canada, H3T 1C5
      • Novo Nordisk Investigational Site
• Croatia
  • Zagreb, Croatia, 10 000
    • Novo Nordisk Investigational Site
  • Zagreb, Croatia, 10000
    • Novo Nordisk Investigational Site
• Czechia
  • Olomouc, Czechia, 779 00
    • Novo Nordisk Investigational Site
  • Pardubice, Czechia, 53203
    • Novo Nordisk Investigational Site
  • Prague 5, Czechia, 15018
    • Novo Nordisk Investigational Site
• India
  • Andhra Pradesh
    • Hyderabad, Andhra Pradesh, India, 500034
      • Novo Nordisk Investigational Site
  • Karnataka
    • Bangalore, Karnataka, India, 560034
      • Novo Nordisk Investigational Site
  • Maharashtra
    • Mumbai, Maharashtra, India, 400008
      • Novo Nordisk Investigational Site
    • Mumbai, Maharashtra, India, 400012
      • Novo Nordisk Investigational Site
  • New Delhi
    • New Dehli, New Delhi, India, 110029
      • Novo Nordisk Investigational Site
  • Tamil Nadu
    • Chennai, Tamil Nadu, India, 600086
      • Novo Nordisk Investigational Site
• Israel
  • Beer Sheva, Israel, 84101
    • Novo Nordisk Investigational Site
  • Haifa, Israel, 31096
    • Novo Nordisk Investigational Site
  • Petah Tikva, Israel, 49202
    • Novo Nordisk Investigational Site
  • Tel Aviv, Israel
    • Novo Nordisk Investigational Site
  • Tel Hashomer, Israel, 52621
    • Novo Nordisk Investigational Site
  • Zerifin, Israel, 70300
    • Novo Nordisk Investigational Site
• North Macedonia
  • Skopje, North Macedonia, 1000
    • Novo Nordisk Investigational Site
• Poland
  • Gdansk, Poland, 80-952
    • Novo Nordisk Investigational Site
  • Warszawa, Poland, 04-730
    • Novo Nordisk Investigational Site
  • Warszawa, Poland, 04-736
    • Novo Nordisk Investigational Site
• Russian Federation
  • Moscow, Russian Federation, 125373
    • Novo Nordisk Investigational Site
  • Novosibirsk, Russian Federation, 630048
    • Novo Nordisk Investigational Site
  • Saint-Petersburg, Russian Federation, 191144
    • Novo Nordisk Investigational Site
  • Tomsk, Russian Federation, 634050
    • Novo Nordisk Investigational Site
  • Ufa, Russian Federation, 450106
    • Novo Nordisk Investigational Site
• Serbia
  • Belgrade, Serbia, 11070
    • Novo Nordisk Investigational Site
  • Nis, Serbia, 18 000
    • Novo Nordisk Investigational Site
  • Novi Sad, Serbia, 21000
    • Novo Nordisk Investigational Site
• Slovenia
  • Ljubljana, Slovenia, 1525
    • Novo Nordisk Investigational Site
• South Africa
  • Gauteng
    • Johannesburg, Gauteng, South Africa, 2193
      • Novo Nordisk Investigational Site
    • Pretoria, Gauteng, South Africa, 0181
      • Novo Nordisk Investigational Site
  • KwaZulu-Natal
    • Mayville, KwaZulu-Natal, South Africa, 4058
      • Novo Nordisk Investigational Site
• Spain
  • Barcelona, Spain, 08035
    • Novo Nordisk Investigational Site
  • Esplugues Llobregat(Barcelona), Spain, 08950
    • Novo Nordisk Investigational Site
  • Leganés, Spain, 28911
    • Novo Nordisk Investigational Site
  • Madrid, Spain, 28046
    • Novo Nordisk Investigational Site
  • Madrid, Spain, 28034
    • Novo Nordisk Investigational Site
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85053
      • Novo Nordisk Investigational Site
    • Tucson, Arizona, United States, 85724
      • Novo Nordisk Investigational Site
  • California
    • Sacramento, California, United States, 95816
      • Novo Nordisk Investigational Site
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Novo Nordisk Investigational Site
  • Florida
    • Jacksonville, Florida, United States, 32207
      • Novo Nordisk Investigational Site
    • Maitland, Florida, United States, 32751
      • Novo Nordisk Investigational Site
    • Melbourne, Florida, United States, 32901
      • Novo Nordisk Investigational Site
    • Tallahassee, Florida, United States, 32308
      • Novo Nordisk Investigational Site
    • Tampa, Florida, United States, 33612
      • Novo Nordisk Investigational Site
  • Georgia
    • Atlanta, Georgia, United States, 30339
      • Novo Nordisk Investigational Site
    • Atlanta, Georgia, United States, 30322
      • Novo Nordisk Investigational Site
  • Idaho
    • Idaho Falls, Idaho, United States, 83404-7596
      • Novo Nordisk Investigational Site
  • Illinois
    • Springfield, Illinois, United States, 62703
      • Novo Nordisk Investigational Site
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Novo Nordisk Investigational Site
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • Novo Nordisk Investigational Site
  • Kentucky
    • Lexington, Kentucky, United States, 40503
      • Novo Nordisk Investigational Site
  • Maryland
    • Baltimore, Maryland, United States, 21229
      • Novo Nordisk Investigational Site
  • Massachusetts
    • Worcester, Massachusetts, United States, 01655
      • Novo Nordisk Investigational Site
  • Missouri
    • Kansas City, Missouri, United States, 64111
      • Novo Nordisk Investigational Site
  • New York
    • Buffalo, New York, United States, 14203
      • Novo Nordisk Investigational Site
  • Oklahoma
    • Tulsa, Oklahoma, United States, 74135
      • Novo Nordisk Investigational Site
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Novo Nordisk Investigational Site
    • Philadelphia, Pennsylvania, United States, 19104
      • Novo Nordisk Investigational Site
  • Texas
    • Dallas, Texas, United States, 75231
      • Novo Nordisk Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 17 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria: - Informed consent obtained before any trial related activities. Trial related activities are any procedures that are carried out as part of the trial, including activities to determine suitability for the trial - Subjects diagnosed with type 1 diabetes mellitus - HbA1c below or equal to 11.0% Exclusion Criteria: - Known hypoglycaemic unawareness or recurrent severe hypoglycaemic events as judged by the investigator - More than 1 episode of diabetic ketoacidosis requiring hospitalisation within the last 3 months prior to Visit 1 (Screening) - Any chronic disorder or significant concomitant disease, which in the investigator's opinion might jeopardise the subject's safety or compliance with the protocol

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Insulin degludec/insulin aspart	Drug: insulin degludec/insulin aspart; Administered subcutaneously (s.c., under the skin) once daily with a main meal. Dose individually adjusted.; Drug: insulin aspart; Administered s.c. with the remaining meals. Dose individually adjusted.; Drug: insulin aspart; Administered s.c. at meal-times. Dose individually adjusted.
Active Comparator: Insulin detemir	Drug: insulin aspart; Administered s.c. with the remaining meals. Dose individually adjusted.; Drug: insulin aspart; Administered s.c. at meal-times. Dose individually adjusted.; Drug: insulin detemir; Administered s.c. once or twice daily. Dose individually adjusted. Subjects will continue with their pre-trial dosing scheme (once (OD) or twice daily (BID)) and will be allowed to switch from OD to BID dosing.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in HbA1c (Glycosylated Haemoglobin) (%)	Percentage point change in glycosylated haemoglobin A1c (HbA1c) from baseline (week 0) to 16 Weeks. Change from baseline summary statistics at week 16 contains only those who had both baseline and week 16 assesment.	Week 0 to week 16

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Fasting Plasma Glucose	Change from baseline in FPG after 16 weeks of treatment. Change from baseline summary statistics at week 16 contains only those who had both baseline and week 16 assesment.	week 0, week 16
Incidence of Treatment Emergent Adverse Events (TEAEs)	A Treatment Emergent Adverse Event (TEAE) was defined as an event with onset date on or after the first day of exposure to randomised treatment and no later than 7 days after the last day on randomised treatment.	After 16 weeks of treatment
Number of Treatment Emergent Confirmed Hypoglycaemic Episodes (Plasma Glucose (PG) Below 3.1mmol/L (56mg/dL) or Severe Hypoglycaemia)	Treatment emergent hypoglycaemic episodes (PG < 3.1 mmol/L (56 mg/dL) or severe hypoglycaemia). Confirmed hypoglycaemic episodes were defined as episodes that were either: Severe (i.e. the child is having altered mental status and cannot assist in their care, is semiconscious or unconscious or in coma with or without convulsions and may require parenteral therapy (glucagon or i.v. glucose), or; An episode biochemically confirmed by PG value of <3.1 mmol/L (56 mg/dL), with or without symptoms consistent with hypoglycaemia.	After 16 weeks of treatment
Number of Treatment Emergent Nocturnal Confirmed Hypoglycaemic Episodes	The confirmed hypoglycaemic episodes occurring between 23:00 and 07:00 were considered for this endpoint	After 16 weeks of treatment
Number of Hyperglycaemic Episodes (PG Above 14.0 mmol/L (250 mg/dL) Where Subject Looks/Feels Ill	The episode of hyperglycaemia was noted when the glucose measurement was 14.0mmol/L or above and the subject looked /felt ill.	After 16 weeks of treatment
Number of Hyperglycaemic Episodes (PG Above 14.0 mmol/L (250 mg/dL) Where Subject Looks/Feels Ill With Ketosis (Blood Ketones Above 1.5 mmol/L)	The episode of hyperglycaemia was noted when the glucose measurement was 14.0mmol/L or above and the subject looked /felt ill. The ketone meaurement involved an additional finger prick and ketosis was considered present if blood ketones were higher than 1.5mmol/L	After 16 weeks of treatment

Collaborators and Investigators

• Sponsor: Novo Nordisk A/S

Publications and helpful links

General Publications

• Thalange N, Deeb L, Klingensmith G, Franco DR, Bardtrum L, Tutkunkardas D, Danne T. The rate of hyperglycemia and ketosis with insulin degludec-based treatment compared with insulin detemir in pediatric patients with type 1 diabetes: An analysis of data from two randomized trials. Pediatr Diabetes. 2019 May;20(3):314-320. doi: 10.1111/pedi.12821. Epub 2019 Feb 10.
• Battelino T, Deeb LC, Ekelund M, Kinduryte O, Klingensmith GJ, Kocova M, Kovarenko M, Shehadeh N. Efficacy and safety of a fixed combination of insulin degludec/insulin aspart in children and adolescents with type 1 diabetes: A randomized trial. Pediatr Diabetes. 2018 Nov;19(7):1263-1270. doi: 10.1111/pedi.12724. Epub 2018 Aug 16.

Helpful Links

• Clinical Trials at Novo Nordisk

Study record dates

Study Major Dates

• Study Start (Actual): October 17, 2013
• Primary Completion (Actual): November 7, 2014
• Study Completion (Actual): November 7, 2014

Study Registration Dates

• First Submitted: April 16, 2013
• First Submitted That Met QC Criteria: April 16, 2013
• First Posted (Estimate): April 19, 2013

Study Record Updates

• Last Update Posted (Actual): June 11, 2019
• Last Update Submitted That Met QC Criteria: June 3, 2019
• Last Verified: June 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1; Hypoglycemic Agents; Physiological Effects of Drugs; Insulin; Insulin, Globin Zinc; Insulin Aspart; Insulin, Long-Acting; Insulin degludec, insulin aspart drug combination; Insulin Detemir
• Other Study ID Numbers: NN5401-3816; 2012-003566-41 (EudraCT Number); U1111-1133-0958 (Other Identifier: WHO); PIP no. be confirmed (Other Identifier: EMA)